1. Field of the Invention
The present invention relates to a process for producing an optically active epoxy compound which is an important intermediate in the synthesis of optically active medicines including benzopyran compounds, etc., for the treatment of hypertension, asthma, etc.
2. Description of the Prior Art
One of the most general methods in case that an epoxy compound is used for preparing optically active medicines is a separation of diastereomer at a further proceeded stage (e.g., to treat amino-alcohol compound obtained by reacting the epoxy compound with ammonia). It is exemplified by the optical resolution of pyranobenzoxadiazole compounds described in Japanese Patent Application Laid-Open No. 141286/1991, EP 409165, and U.S. Pat. No. 5,097,037, and also by the synthesis of optically active indene oxide described in J. Med. Chem. 35, 1685-1701 (1992). There is another method which involves the step of making a halohydrin compound (as a precursor of an epoxy compound) into its derivatives and conducting the separation of the diastereomer on it at that step, or which resorts to the stereoselectivity of an enzyme. An example is the optical resolution of benzopyran compounds, which is described in Circulation Research, 62, 4, 679-686 (1988). The foregoing two methods, however, suffer a serious economical disadvantage that as they separate racemic mixture, enantiomer which is not used become completely wasted.
There has recently been found a new process for synthesis which employs an optically active manganese complex as an asymmetric catalyst. This process is attracting attention because of its ability to yield optically active epoxy compounds effectively. Examples of the asymmetric catalyst are given by Jacobsen et al. in J. Am. Chem. Soc., 113, 7063-7064, (1991) and also by Katsuki in Japanese Patent Application Laid-Open No. 301878/1993 and European Patent Laid-Open No. 535377. Unlike the separation of racemic mixture, this process solved the problem that enantiomer which is not used becomes wasted. Therefore, it affords high chemical and optical yields if appropriate olefins are selected as the starting material. However, the catalysts reported so far are not satisfactory for the production of every optically active epoxy compound. Active researches are under way for further improvement.
After the present inventors have conducted their intensive researches, they have found out a process for producing optically active epoxy compounds by using olefin compounds which do not have functional group coordinating with metals such as hydroxy group at the neighbor of a double bond. (Said olefin compounds are hereinafter referred to as "unfunctionalized olefin compound" or "olefin compound having no precoordinating functional group".)